Engagement of the T cell receptor (TCR) with MHC-peptide complexes leads to the activation of protein tyrosine kinases (PTK), ultimately leading to the activation of downstream signaling events, such as calcium flux and mitogen-activated protein kinase (MAPK) activation (Chan et al. 1994). For many years, it was observed that a 36–38 kDa protein, localized to the plasma membrane, was highly tyrosine phosphorylated upon ligation of the TCR and associated with Grb2, PLC-γ1, and the p85 subunit of PI3K. It was hypothesized that this protein served as a critical link connecting TCR engagement at the membrane to activation of signaling events in the cytosol. In 1998, the gene encoding this protein was identified after microsequencing phosphorylated proteins purified from the membrane fractions of activated Jurkat T cells and was named LAT, linker for activation of Tcells. Sequencing of cDNA clones revealed that LAT is a type III transmembrane protein that contains a...
- Wang Y, Kissenpfennig A, Mingueneau M, Richelme S, Perrin P, Chevrier S, et al. Th2 lymphoproliferative disorder of LatY136F mutant mice unfolds independently of TCR-MHC engagement and is insensitive to the action of Foxp3+ regulatory T cells. J Immunol. 2008;180:1565–75.PubMedPubMedCentralCrossRefGoogle Scholar
- Zhang W, Trible RP, Zhu M, Liu SK, McGlade CJ, Samelson LE. Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell angigen receptor-mediated signaling. J Biol Chem. 2000;275:23355–61.PubMedPubMedCentralCrossRefGoogle Scholar